There is an increasing demand in the cosmetics industry to develop products that may be applied topically to the skin that improve the condition and appearance of skin. Consumers are interested in mitigating or delaying the dermatological signs of chronologically- or hormonally-aged skin, as well as skin aging due to the environmental stress, such as fine lines, wrinkles, sagging skin and other conditions due to a progressive loss of cell growth, proliferation and functionality in the epidermal and dermal skin layers. During the aging process, the complexion of the skin, i.e., the color and appearance of the skin, deteriorates slowly from aging and/or exposure to environmental stress, e.g., sunlight.
There remains a general need in the cosmetics industry for products that retard or counter the aging effects on the skin, and more specifically for products that produce such effects without undesirable side effects. In particular, there remains a need for topically applied cosmetic compositions that provide anti-aging and skin texture benefits using natural plant materials as active components.
Active ingredients or components derived or extracted from plants and plant seeds have commonly been employed for a myriad of medicinal, therapeutic and cosmetic purposes. Such actives may be obtained from the entire plant or various parts of a plant, such as seeds, needles, leaves, flowers, roots, bark, cones, stems, rhizomes, callus cells, protoplasts, and meristems. Active ingredients or components are incorporated in compositions in a variety of forms. Such forms include a pure or semi-pure component, a solid or liquid extract or derivative, or a solid natural plant material. Plant material may be incorporated in a variety of subforms such as whole, minced, ground or crushed, or otherwise physically modified for incorporation into a composition.
MAGP-1 (Microfibril-associated glycoprotein 1) is a small glycine rich acidic protein in extra-cellular matrix (ECM). MAGP-1 is a 30-33 kDa member of the microfibril associated glycoprotein family of proteins. It was found to be a key component of microfibrils and elastic fibers in skin. MAGP-1 forms complexes with other microfibril proteins such as fibrillin. Besides providing structural support for skin elastic fiber formation, MAGP-1 is also essential for vascular integrity, wound healing, and proper body fat deposition, possibly through regulating TGF-beta signaling, based on animal studies. MAGP-1 apparently mediates the release of Notch extracellular domain and also likely binds to type IV collagen and contributes to elastin fiber formation.
The present invention identifies a number of compounds and/or plant materials and extracts found to be active at simulating expression of the extracellular matrix protein MAGP-1. Among the plant materials, which preferably are in the form of extracts, are Sesbania grandiflora, Antidesma bunius, Operculina turpethum, Ixora chinensis, Clerodendron lindleyi, Amorphophallus campanulatus, Tiliacora triandra, and Thunbergia laurifolia. Suitable compounds are the tetrapeptide lysine-threonine-phenylalanine-lysine (Lys-Thr-Phe-Lys) (herein KTFK), thiodipropionic acid (TDPA) and its lower alkyl mono- and diesters, a substituted 2-(2-benzyl-1-benzimidazoyl)acetamide analog having the structure:
and an N-substituted sulfonyloxybenzylamine having the structure:

Certain of the MAGP-1 active plant species, namely, Antidesma bunius, Operculina turpethum, Ixora chinensis, and Clerodendron linleyi, including extracts of these plant species, have not been previously known for topical application to skin to improve the skin's aesthetic appearance. Similarly, the above-disclosed substituted 2-(2-benzyl-1-benzimidazoyl)acetamide analog and the N-substituted sulfonyloxybenzylamine as disclosed above have not been known previously for topical application to skin to improve the skin's aesthetic appearance.
Antidesma bunius is a species of fruit tree in the spurge family. It is native to Southeast Asia, the Philippines, and northern Australia. Its common Philippine name and other names include bignay, bugnay or bignai and currant tree. This is a variable plant which may be short and shrubby or tall and erect, approaching 30 meters in height. It has large oval shaped leathery evergreen up to about 20 centimeters long and seven wide. The leaves are sudorific and employed in treating snakebite, in Asia. (Morton, J. 1987. Bignay. p. 210-212. In: Fruits of warm climates. Julia F. Morton, Miami, Fla.).
Operculina turpethum is a plant in the morning glory family, (syn. Ipomoea turpethum) and is known commonly as turpeth, fue vao, and St. Thomas lidpod. It is one of many plants mentioned in the literature having claims of activity against liver disorders. Vasudesan, N, V., Indian Medicinal Plants, Vol. IV, Orient Longman Ltd, Chennai, 1995, 172. It also has anthelmintic expectorant, antipyretic, anti-inflammatory and purgative properties. Id.
Ixora chinensis is a fairly small, bushy shrub, usually only 5-10 ft tall. There are dwarf varieties that are much smaller. Ixora will flower when only a few inches high. It is commonly used a hedge or small garden plant. The plant is mainly grown as ornamental but its flowers are believed to have some medicinal uses including treatment for hypertension and for treating rheumatism, abscesses, bruises and wounds. The plant is native to India and Sri Lanka
Clerodendron lindleyi are shrubs, lianas, and small trees, usually growing to 1-12 m tall, with opposite or whorled leaves. The genus is native to tropical and warm temperate regions of the world, with most of the species occurring in tropical Africa and southern Asia, but with a few in the tropical Americas and northern Australasia, and a few extending north into the temperate zone in eastern Asia. Clerodendrum is from the Greek, meaning “lottery tree”. Dendros meaning tree. The lottery refers to unsure possibility of medicinal value from certain plants of this genus.
Sesbania grandiflora (also known as agati, syn. Aeschynomene grandiflora) or hummingbird tree/scarlet wisteria is a small tree in the genus Sesbania. It is a fast-growing tree with a typical adult height of between 3 and 5 m. The leaves are regular and rounded and the flowers white and large, very characteristic. The fruits look like flat, long and thin green beans. The tree thrives under full exposure to sunshine and is extremely frost sensitive. It is believed to have originated either in India or Southeast Asia and grows primarily in hot and humid tropical areas of the world. Bark, leaves, gums, and flowers are considered medicinal. The astringent bark was used in treating smallpox and other eruptive fevers. (James A. Duke. 1983. Handbook of Energy Crops. unpublished.) Sesbania grandiflora was previously disclosed in U.S. Pat. No. 7,618,662, the disclosure of which is incorporated herein by reference.
Thunbergia laurifolia or Blue trumpet vine is an invasive species, which is used like an ornamental plant. This plant is found in Cerrado vegetation of Brazil. In Malaysia, juice from crushed leaves of T. laurifolla are taken for menorrhagia, placed into the ear for deafness, and applied for poulticing cuts and boils (Burkill, I. H. (1966). “A Dictionary of the Economic Products of the Malay Peninsula. Volume II (I-Z)”. Ministry of Agriculture and Cooperatives, Kuala Lumpur.). In Thailand, leaves are used as an antipyretic, as well as an antidote for detoxifying poisons (Kanchanapoom, T. et al. (2002). “Iridoid glucosides from Thunbergia laurifolia”. Phytochemistry 60: 769-771).
KTFK is a synthetic tetrapeptide lysine-threonine-phenylalanine-lysine (Lys-Thr-Phe-Lys), known to be active in collagen and fibronectin synthesis. KTFK was previously disclosed in U.S. Patent Application Publication No. 2004/0126344, the disclosure of which is incorporated herein by reference.
Amorphophallus campanulatus is found in tropical regions from Madagascar to Asia, Polynesia and northern Australia. The root is carminative, restorative, stomachic and tonic. Chopra. R. N., Nayar. S. L. and Chopra. I. C. Glossary of Indian Medicinal Plants (Including the Supplement). Council of Scientific and Industrial Research, New Delhi. 1986; Medicinal Plants of Nepal Dept. of Medicinal Plants. Nepal. 1993. It is dried and used in the treatment of piles and dysentery. Id. The fresh root acts as an acrid stimulant and expectorant, it is much used in India in the treatment of acute rheumatism. Id. Amorphallus campamilatus was previously disclosed in U.S. Pat. No. 7,618,862, the disclosure of which is incorporated herein by reference.
Thiodopropionic acid (TDPA) is white crystalline solid having a slight characteristic odor and has demonstrated some antimicrobial and antioxidants activity. (WHO/Food Add/24.65 FAO Nutrition Meetings Report Series No. 38A). Thiodopropionic acid and its esters was previously disclosed in U.S. Patent Application Publication No. 2004/0126344, the disclosure of which is incorporated herein by reference.
Sapindus rarak is part of the Sapindus genus comprising about five to twelve species of shrubs and small trees in the Lychee family, Sapindaceae, native to warm temperate to tropical regions in both the Old World and New World. The extract of Sapindus rarak has demonstrated analgesic effects. Sapindus rarak was previously disclosed in U.S. Pat. No. 7,514,092, the disclosure of which is incorporated herein by reference.
Tiliacora triandra Diels of the Tiliacora family, also known as Yanang, is a species of flowering plant native to mainland Southeast Asia and used particularly in the cuisines of northeast Thailand and Laos. It is a climbing plant with mostly single, smooth, oval-shaped, deep green leaves and yellowish flowers. In traditional Southeast Asian medicine, Tiliacora triandra has been used as an herbal medicine for fever relief, alcohol intoxication, inflammation, and bacterial/fungal infection. For instance, the use of Tiliacora triandra Diels against plasmodium falciparum (cause malaria in humans) is disclosed in Pavanand et al., Phytother. Res., 3, 215-217 (1989). Tiliacora triandra is the subject of a separate application filed concurrently with the instant application.
Safe, effective and new components of compositions to treat, prevent, reduce, inhibit and/or improve the dermatological signs of aging, including environmental stress, due to a progressive degradation of the epidermal and dermal skin layers, would be advantageous for the formulation of treatments and products for the skin. As described herein, novel and beneficial methods and compositions, as well as their mode of action, for the treatment of wrinkles and the like, as well as for personal care products for the skin, are provided herein.